The work of our group is concerned with the control of plasticity in the adult nervous system and its pathological and pharmacological alterations. As a world expert in the study of the serotonin 5-HT2B serotonin receptor, after having made major contributions to the demonstration of the role of this receptor in the cardiovascular system, we have moved our interest in characterizing its function in the brain.
During the past years, our research group has successfully demonstrated a previously unsuspected role of 5-HT2B receptor in the nervous system. We have participated in a collaborative effort to demonstrate that a loss of function SNP in the 5-HT2B receptor gene (HTR2B) was associated with psychiatric diseases marked by high impulsivity and suicidal behavior in humans. We showed that Htr2B−/− mice displayed also increased impulsive behaviors, in particular in delayed discounting tasks. We have also shown that these receptors contribute to the behavioral and physiological effects of amphetamine derivatives and 5-HT releasers. We then evidenced the need for these receptors for the antidepressant effects of SSRIs as a positive serotonergic autoreceptor.
On the other hand, our data show that microglia in Htr2b-/- mice differ from those of wild-type mouse in their activation state, indicating that the 5-HT2B receptor modulates the microglial response and suggesting a protective role of this receptor against excessive neuroinflammation. We suggest that the serotonin-microglia interaction controls neuroinflammation and illness behavior, and that deregulation of this pathway is involved in some psychiatric disorders.
Our work now intends to unravel links between the serotonin and dopamine system in relation to impulsivity, depression, and inflammation and to identify the cellular basis of these actions (dopamine and/or serotonin neurons and/or microglia).